Functional association of the β1 subunit with human cardiac (hH1) and rat skeletal muscle (μ1) sodium channel α subunits expressed in Xenopus oocytes

H. Bradley Nuss, Nipavan Chiamvimonvat, M. Teresa Pérez-García, Gordon F. Tomaselli, Eduardo Marbán

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


Native cardiac and skeletal muscle Na channels are complexes of α and β1 subunits. While structural correlates for activation, inactivation, and permeation have been identified in the α subunit and the expression of α alone produces functional channels, β1-deficient rat skeletal muscle (μ1) and brain Na channels expressed in Xenopus oocytes do not gate normally. In contrast, the requirement of a β1 subunit for normal function of Na channels cloned from rat heart or human heart (hH1) has been disputed. Coinjection of rat brain β1 subunit cRNA with hH1 (or μ1) α subunit cRNA into oocytes increased peak Na currents recorded 2 d after injection by 240% (295%) without altering the voltage dependence of activation. In μ1 channels, steady state inactivation was shifted to more negative potentials (by 6 mV, p < 0.01), but the shift of 2 mV was not significant for hH1 channels. Nevertheless, coexpression with β1 subunit speeded the decay of macroscopic current of both isoforms. Ensemble average hH1 currents from cell-attached patches revealed that coexpression of β1 increases the rate of inactivation (quantified by time to 75% decay of current; p < 0.01 at - 30, -40, and -50 mV). Use-dependent decay of hH1 Na current during repeated pulsing to -20 mV (1 s, 0.5 Hz) after a long rest was reduced to 16 ± 9% of the first pulse current in oocytes coexpressing α and β1 subunits compared to 35 ± 8% use-dependent decay for oocytes expressing the α subunit alone. Recovery from inactivation of μ1 and hH1 Na currents after 1-s pulses to - 20 mV is multiexponential with three time constants; coexpression of β1 subunit decreased all three recovery time constants. We conclude that the β1 subunit importantly influences the function of Na channels produced by coexpression with either the hH1 or β1 α subunits.

Original languageEnglish (US)
Pages (from-to)1171-1191
Number of pages21
JournalJournal of General Physiology
Issue number6
StatePublished - Dec 1995
Externally publishedYes

ASJC Scopus subject areas

  • Physiology


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